Corticotropin-releasing factor neurons in the hypothalamic paraventricular nucleus are involved in arousal/yawning response of rats.

Our previous studies have suggested that activation of the hypothalamic paraventricular (PVN) descending oxytocinergic projections is involved in the induction of yawning accompanied by an arousal response, but the possibility that neural systems other than the oxytocinergic system in the PVN also mediate the arousal/yawning response cannot be ruled out. We assessed the activity of corticotropin-releasing factor (CRF) neurons during yawning induced by the PVN stimulation in anesthetized, spontaneously breathing rats using double-staining for c-Fos and CRF. Yawning response was evaluated by monitoring an intercostals electromyogram as an index of inspiratory activity and a digastric electromyogram as an indicator of mouth opening. We also recorded the electrocorticogram (ECoG) to determine the arousal response during yawning. Microinjection of l-glutamate (2-5 nmol) into the PVN produced a frequent yawning accompanied by an arousal shift in the ECoG, and these behavioral effects were associated with a significant increase of c-Fos positive CRF neurons in the medial parvocellular subdivision of the PVN. In addition, a marked enhancement in the c-Fos expression was found in the both locus coeruleus (LC) and global area in the cortex when the frequency of yawning response was increased by the PVN stimulation, suggesting that the arousal response during yawning might be mediated by the activation of LC neurons. The present study suggests that an activation of CRF neurons in the PVN is responsible for the arousal response accompanied by yawning behavior.

In vivo nitric oxide concentration in the vitreous of rat eye.

Nitric oxide (NO) has been proposed to mediate light-adaptation in the vertebrate retina. However, the in vivo NO concentration in the retina is not known. We measured NO in the vitreous adjacent to the retina of the rat eye using NO-selective electrodes under various light conditions. The rats were kept under a 12:12 h light/dark cycle with lights on from 08:00 to 20:00 h. NO during the daytime in the light remained constant at 0.85+/-0.41 microM (n=10), and decreased after dark-adaptation, while NO during the nighttime in darkness was 0.55+/-0.27 microM (n=5), and increased in the light. The vitreous NO initially increased rapidly to flicker, but then decreased as the flicker continued. We found that the diurnal change of NO in the vitreous depended on the ambient light condition.

Light induces cortical activation and yawning in rats.

We examined the effects of light stimulation on cortical activation and yawning response in anesthetized, spontaneously breathing rats. Cortical activation was assessed by means of an electrocorticogram (ECoG) and yawning response was evaluated by monitoring an intercostal electromyogram as an index of inspiratory activity and a digastric electromyogram as an indicator of mouth opening. Light stimulation elicited an arousal shift in the ECoG to faster rhythms. This arousal response was followed by a single large inspiration with mouth opening, i.e. a yawning response. Higher light intensity significantly reduced the onset latency of the arousal/yawning response. Pretreatment with pyrilamine, an H1-histamine receptor antagonist, injected into the lateral ventricle blocked both the cortical activation and the yawning response induced by light stimulation, suggesting a role of brain histaminergic neurotransmission in modulating the light-induced arousal/yawning responses.

Yawning/cortical activation induced by microinjection of histamine into the paraventricular nucleus of the rat.

The effects of microinjection of histamine into the paraventricular nucleus (PVN) of the hypothalamus on yawning responses were investigated in anesthetized, spontaneously breathing rats. Yawning responses were evaluated by monitoring the intercostal electromyogram (EMG) as an index of inspiratory activity and digastric EMG as an indicator of mouth opening. We also recorded the electrocorticogram (ECoG) to determine the arousal response during yawning. Autonomic function was evaluated by measuring blood pressure and heart rate. Microinjection of histamine into the medial parvocellular subdivision (mp) of the PVN elicited a yawning response, i.e. a single large inspiration with mouth opening, and an arousal shift in ECoG to lower voltage and faster rhythms. Microinjection of HTMT dimaleate, an H1 receptor agonist, into the PVN also caused the yawning/arousal response. Pretreatment with pyrilamine, an H1 receptor antagonist, inhibited the histamine induced yawning behavior. These data demonstrate that a histamine receptive site for triggering yawning/arousal responses exists in the PVN, and suggest that these responses are mediated by activation of H1 receptor within the PVN.

Cortical arousal induced by microinjection of orexins into the paraventricular nucleus of the rat.

Orexin-A is a neuropeptide which has been suggested to be involved in sleep and arousal mechanisms. Orexin-A, for example, stimulates arousal when administrated intracerebroventricularly to rats. We attempted to identify specific neural sites of orexin-A and orexin-B action. Orexin-A and orexin-B were microinjected into the medial parvocellular subdivision of the paraventricular nucleus (PVN) in anesthetized, spontaneously breathing rats, and cortical arousal and yawning responses were assessed. Cortical arousal responses were monitored with the electrocorticogram (ECoG), and yawning responses were evaluated by monitoring intercostal electromyograms as an index of inspiratory activity and digastric electromyograms as an indicator of mouth opening. We also measured blood pressure and heart rate during yawning responses, since yawning is accompanied by changes in autonomic activity. Microinjection of orexin-A into the PVN elicited an arousal shift in the ECoG to lower voltage and faster rhythms. This cortical arousal response was followed by a single large inspiration with mouth opening, i.e. a yawning response. On the other hand, microinjection of orexin-B into the PVN elicited an arousal shift in the ECoG without yawning responses. These results demonstrate that an orexin receptive site for triggering arousal/yawning responses exists in the PVN, and suggest that the PVN is involved in arousal mechanisms.